Government incentives likely will be necessary to rejuvenate the development pipeline for antibiotics, Janet Woodcock, director of FDA's Center for Drug Evaluation and Research, told a congressional committee.

The number of investigational new drug applications for antibiotics has declined since 1987, but has started to increase again over the last three years, Woodcock told the House Energy and Commerce Committee, Subcommittee on Health June 9. But as more bacteria develop a resistance to antibiotics, she said more and new therapies are necessary.

Drug-resistant infections cost $35 billion a year in the United States, yet many companies do not find antibiotics a financially viable product, since they involve a limited course of treatment and have generic competition, among other factors.

There also is confusion among the scientific pathway for approval. Woodcock said a new guidance on clinical trial designs is in the works, but acknowledged that the clarity from the document alone may not be enough to push the industry to increase drug development.

"It will likely also take the development of incentives in order to stimulate the development of new antibacterial drugs so that we have new therapeutic options to treat the resistant pathogens that we currently face and the resistant pathogens that we will face in the years ahead," Woodcock said in written testimony.

Recognizing that government intervention is necessary to help solve the problem is a giant step forward, said Barry Eisenstein, senior vice president, scientific affairs, Cubist Pharmaceuticals, who also testified at the hearing.

Cubist, which Eisenstein said he considers a mid-cap company, has three antibiotic drugs in development, and its Cubicin (daptomycin) drug was approved in 2003 to treat skin infections caused by methicillin-resistant staphylococcus aureus (MRSA) and other bacteria.

"To me this is almost a break-through to see a branch of government actually saying: 'You know what? We really do have market failure, we need government intervention in a meaningful way,'" Eisenstein said in an interview after the hearing. "To see the FDA actually step up to the plate, going essentially above and beyond what they needed to do to make that comment, just underscores the great need that we have."

Several ideas already have been discussed, including tax incentives for research (Also see "Financial Incentives Seen As A Path To Resurgence Of Antibiotics" - Pink Sheet, 26 April, 2010.).

During his testimony, Eisenstein policies for antibiotics modeled on the programs that have sparked development of drugs for rare diseases and expanded the knowledge about pediatric uses. He listed guaranteed market contracts, priority review vouchers for applications, and product development grants among his strategies, but said other ideas are needed.

"New incentives must be designed so that they encourage investment in activities across the research spectrum, from basic research to clinical trials, and target as broad a range of scientists, entrepreneurs, large and small companies, and life science investors as possible," Eisenstein said in written testimony.

Woodcock warned that incentives still have to be considered in the context of restrictions that may be required once the drugs are on the market because the ultimate goal is limiting antibiotic use.

"If we contemplated a pipeline that would end up (where) antimicrobials would only be used in niche situations, where they were really needed, that would be even a further disincentive," she said. "But you have to think about that as a goal to preserve the effect of that for a long time."

Development Through Liability And Anti-Trust Laws

Robin Robinson, director of the Biomedical Advanced Research and Development Authority, said industry has indicated in the past that liability protections would be very helpful and important in moving drugs along the pipeline.

Robinson and Woodcock also said an idea of easing anti-trust laws in certain cases to encourage companies to work together was worth exploring. Robinson said BARDA used the authority in the development of the H5N1 and H1N1 influenza vaccines and certainly could try it again.

"I have worked in public-private partnerships where we have gotten companies together to advance general societal goals and they've had to be extremely lawyer-intensive on the anti-trust issue," Woodcock said. "So there's no doubt I think it's a barrier to working together to advance broader goals."

Questioning The Excellence In Exclusivity

Addressing the pediatric and orphan drug exclusivity examples, Subcommittee chairman Frank Pallone, D-N.J., said did not entirely understand how effective the government could be by offering the industry incentive and yet still encourage the limited use of antibiotics.

"Explain how six months or even two years of exclusive marketing would result in companies investing in antibiotic development, when as I mentioned the only way to preserve an antibiotic's effectiveness is to minimize its use," Pallone said.

Brad Spellberg, associate professor of medicine at UCLA's David Geffen School of Medicine, who represented the Infectious Diseases Society of America, said one incentive will not be enough to fix the problem. ISDA's desired exclusivity goes well beyond the rewards offered under existing programs, however: the association feels that 15 to 20 years of exclusivity should be made available

Even with that kind of exclusivity, "a panel of push and pull incentives, which can appeal to the various constituents ... active along the entire R&D spectrum, must be created," Spellberg said in written testimony.

Jeffrey Levi, executive director of Trust for America's Health, said exclusivity will play a role, but it is not clear on how major a role.

"Will that be enough to bring big manufacturers to the table?" Levi said. "We need both the intellectual capital that these companies have and the production and marketing capacity that they have."

-Derrick Gingery (d.gingery@elsevier.com)

Antibiotics Need Additional Development Incentives, FDA Says

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